Gadolinium-based compound, method for producing same, and MRI contrast agent containing same

Abstract

The present invention relates to a novel gadolinium-based compound having a structure in which a gadolinium complex and a gallic acid are bonded to each other, a method for producing same, and an MRI contrast agent containing same.

What is claimed is: 
     
         1 . A gadolinium-based compound represented by a following Chemical Formula 1: 
       
         
           
           
               
               
           
         
         wherein in the Chemical Formula 1, 
         A represents *—(CH 2 ) n -A 1 -*, 
         n represents any integer from 0 to 5, 
         A 1  represents *—COO—*, *—CO—*, *—NH—*, *—CH 2 —*, *—CONH—*, or *—O—*, 
         Linker represents *-L 1 -NHCO-L 2 -*, *-L 1 -O—R—O-L 2 -*, *-L 1 -CH 2 -L 2 -*, *-L 1 -NH-L 2 -*, or *-L 1 -COO-L 2 -*, 
         L 1  represents linear or branched (C1-C30)alkyl, 
         L 2  represents a single bond, hydrogen or linear or branched (C1-C30)alkyl, 
         R represents linear or branched (C1-C20)alkyl, 
         Ga represents a following Chemical Formula 2: 
       
       
         
           
           
               
               
           
         
         * indicates a connection site. 
       
     
     
         2 . The gadolinium-based compound of  claim 1 , wherein n represents any integer from 1 to 5, and A 1  represents *—CONH—*. 
     
     
         3 . The gadolinium-based compound of  claim 1 , wherein L 1  represents linear or branched (C1-C10)alkyl, and L 2  represents the single bond. 
     
     
         4 . The gadolinium-based compound of  claim 1 , wherein the gadolinium coordinates with at least one water molecule. 
     
     
         5 . The gadolinium-based compound of  claim 1 , wherein the compound specifically binds to mammalian amyloid beta polymer. 
     
     
         6 . An MRI contrast agent comprising the gadolinium-based compound of  claim 1 . 
     
     
         7 . The MRI contrast agent of  claim 6 , wherein the agent is used for diagnosis of a degenerative brain disease. 
     
     
         8 . The MRI contrast agent of  claim 7 , wherein the agent is used for diagnosis of Alzheimer's disease. 
     
     
         9 . A method for preparing the gadolinium-based compound of  claim 1 , the method comprising following steps:
 (a) reacting a compound represented by a following Chemical Formula 1-1 with a halogen compound to obtain a following Chemical Formula 1-2:   
       
         
           
           
               
               
           
         
         wherein in each of the Chemical Formulas 1-1 and 1-2, 
         PT 1  represents a protecting group, 
         X represents a halogen atom, 
         L 2  is the same as defined in  claim 1 ; 
         (b) reacting the compound of the Chemical Formula 1-2 with a compound represented by a following Chemical Formula 1-3 to obtain a compound represented by a following Chemical Formula 1-4: 
       
       
         
           
           
               
               
           
         
         wherein in each of the Chemical Formulas 1-3 and 1-4, 
         each of PT 1  and PT 2  individually represents a protecting group, 
         Linker represents *-L 1 -NH-L 2 -*, 
         each of L 1 , L 2 , and A is the same as defined in  claim 1 ; 
         (c) removing PT 1  and PT 2  from the compound of the Chemical Formula 1-4; and 
         (d) reacting a compound obtained in the step (c) with gadolinium hydrate to obtain the compound of the Chemical Formula 1. 
       
     
     
         10 . The method of  claim 9 , wherein in the step (a), L 2  represents the single bond, and the halogen compound is thionyl chloride. 
     
     
         11 . A method for preparing the gadolinium-based compound of  claim 1 , the method comprising following steps:
 (a) reacting a compound represented by a following Chemical Formula 2-1 with a compound represented by a following Chemical Formula 2-2 to obtain a following Chemical Formula 2-3:   
       
         
           
           
               
               
           
         
         wherein in each of the Chemical Formulas 2-1 to 2-3, 
         PT 3  represents a protecting group, 
         Linker represents *-L 1 -NH-L 2 -*, 
         each of L 1 , L 2 , and A is the same as defined in  claim 1 ; 
         (b) removing PT 3  from the compound of the Chemical Formula 2-3; and 
         (c) reacting a compound obtained in the step (b) with gadolinium hydrate to obtain the compound of the Chemical Formula 1. 
       
     
     
         12 . The method of  claim 11 , wherein in the step (a), L 2  represents the single bond.